tbuckley/cabot-search huggingface dataset:
POS0424 CHARACTERIZATION OF THE INFLAMMATORY PROTEOME OF SYNOVIAL FLUID FROM PATIENTS WITH PSORIATIC ARTHRITIS: POTENTIAL TREATMENT TARGETS
Authors: N. Barbarroja Puerto, M. D. López Montilla, L. Cuesta López, C. Perez-Sanchez, M. Ruiz-Ponce, C. López-Medina, M. L. Ladehesa Pineda, C. Lopez-Pedrera, A. Escudero Contreras, E. Collantes Estevez, I. Arias de la Rosa
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Synovial membrane inflammation, driven by effector T-cell activation and altered inflammatory cytokine expression, is a key feature of this psoriatic arthritis. The proximity extension assay (PEA) technique could contribute to identifying novel protein biomarkers associated with PsA and to improving the biological understanding and the future management of PsA, leading to novel intervention targets. <h3>Objectives</h3> 1) To characterize the inflammatory proteome of synovial fluid (SF) from patients with Psoriatic Arthritis (PsA) using a next generation proteomics technique, and 2) to evaluate its potential to stratify patients according to clinical features. <h3>Methods</h3> Inflammatory proteome profile of SF from thirteen PsA patients with active knee arthritis were analysed using PEA technology (Olink Target 96 Inflammation panel, Cobiomic Biosciences). Four patients with OA were included as control group. <h3>Results</h3> Seventy-nine inflammation-related proteins were detected in SF from PsA patients (SF-PsA). Unsupervised analyses of the molecular proteome profile in SF-PsA identified two specific phenotypes characterized by higher or lower levels of inflammation-related proteins. Clinically, SF-PsA with higher levels of inflammatory proteins also showed increased systemic inflammation and altered glucose and lipid metabolisms. Besides, SF from PsA patients showed 39 out of 79 proteins significantly altered compared to SF-OA specifically related to cell migration and inflammatory response. Among these, molecules such as TNFα, IL-17A, IL-6, IL-10, IL-8, ENRAGE, CCL20, TNFSF-14, OSM, IFNγ, MCP-3, CXCL-11, MCP4, CASP-8, CXCL-6, CD-6, ADA, CXCL-10, TNFβ and IL-7 showed the most significantly alteration. <h3>Conclusion</h3> This is the first study that characterizes the inflammatory landscape of synovial fluid of PsA patients by analyzing a panel of 92 inflammatory proteins using PEA technology. Novel SF proteins have been described as potential pathogenic molecules involved in the pathogenesis of PsA. Despite the flare, inflammatory proteome could distinguish two different phenotypes related to systemic inflammation and lipid and glucose alterations. <h3>Acknowledgements:</h3> Funded by ISCIII (PI20/00079 and RD21/0002/0033) co-financed by ERDF. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0793-HPR OBSERVATIONAL STUDY IN REAL CLINICAL PRACTICE OF THE TREATMENT OF NON-INFECTIOUS UVEITIS
Authors: M. D. M. Esteban-Ortega, M. Steiner, C. Andreu-Vázquezc, I. Thuissard Vasallo, A. Dóiaz-Rato, S. Muñoz-Fernández
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Uveitis is an ocular disease that is a major cause of morbidity and blindness in the developed world. Although Immunosuppressive drugs and biologic therapy have been shown to be effective in their treatment there are no clear protocols for their use. <h3>Objectives</h3> To describe the characteristics of patients with uveitis associated with immunologic or idiopathic disease who require immunosuppressive treatment and their response in real clinical practice. <h3>Methods</h3> Observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with uveitis associated with immunologic or idiopathic diseases attended in a multidisciplinary consultation between January 2011 and February 2022. To assess the response to treatment, we evaluated the change in visual acuity and vitritis and the presence of macular edema. <h3>Results</h3> We included 356 patients (mean age at diagnosis 42.8 ± 15.8 years, 50% female). Of the total, 157 (44%) had a single flare and 164 (46%) more than three. The involvement was bilateral in 85 patients (24%) and anterior (73%) and idiopathic (43%) were the most frequent. Twelve percent required treatment with systemic corticosteroids and 66 patients (18.5%) immunosuppressive/biological treatment, methotrexate being the most used (55%). Ten patients of the 66 (15%) started treatment with biologics and 34 (48%) required them at some point during the disease, adalimumab being the most used. Thirty-five patients (53%) needed to change drug due to lack of response. There were no differences between different drugs in the resolution of vitritis and improvement of vision. Disappearance of macular edema was achieved in all patients treated with tocilizumab. <h3>Conclusion</h3> The use of systemic corticosteroids and immunosuppressive/biologics was necessary in a high number of patients with non-infectious uveitis. In our series tocilizumab proved to be significantly more effective in the resolution of macular edema. <h3>Reference</h3> [1]Gómez-Gómez A, Loza E, Rosario MP, Espinosa G, de Morales JMGR, Herrera JM, et al. Efficacy and safety of immunomodulatory drugs in patients with non-infectious intermediate and posterior uveitis, panuveitis and macular edema: A systematic literature review. Seminars in Arthritis and Rheumatism. 2020;50(6):1299-306. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0199-PARE RHEUMATOLOGICAL PATIENTS’ KNOWLEDGE OF, BELIEFS ABOUT, AND PRACTICES IN USING PHYTOTHERAPY: AN EXPLORATORY STUDY
Authors: T. Demirci Yildirim, F. Basibuyuk, M. Birlik
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Phytotherapy has emerged as a new concept and has quickly and widely spread in recent years. Studies on phytopharmaceuticals in rheumatology practice are very limited. <h3>Objectives</h3> In this study, we aimed to examine the knowledge of, beliefs about, and practices in using phytotherapy in patients who use biological agents, which we can classify as the last and most potent step in treating rheumatological diseases. <h3>Methods</h3> In the first part of the questionnaire, there are 11 questions including the demographic data of the person, and in the second part, there are 17 questions that aim to learn the level of knowledge about phytotherapy and the use of phytopharmaceuticals. The questionnaire was administered face-to-face to patients with rheumatology using biological therapy who gave consent to participate. <h3>Results</h3> The questionnaire was completed by 100 patients, 51 of them women. The mean age was 39±9 years. 39% of the patients were postgraduate and 23% were at the high school. Of the participants, 45 were diagnosed with ankylosing spondylitis(AS) and 29 with rheumatoid arthritis(RA). The duration of rheumatologic disease was 12.2 years All patients were followed up with biological therapy, 35% were using infliximab and 15% were using adalimumab. The mean duration of biological treatment was 6 years. Of the 100 participants, 60% had information about phytotherapy, and 35 of them had obtained it from social media and television. In general, participants had a positive opinion about phytotherapy, and most didn't obtain approval from their physicians for the use of phytotherapy. Among phytopharmaceutical, participants mostly used green tea(30%), linden(27%), centaury(26%), curcumin(20%). There were 5 participants who experienced side effects related to the use of phytopharmaceuticals. 68% of the patients thought that phytopharmaceuticals had fewer side effects than biological therapy. 55 patients said that they would not use biological therapy if cured with phytopharmaceutical use. <h3>Conclusion</h3> It is inevitable that patients with chronic diseases want to use phytopharmaceuticals, as determined in our questionnaire results. Healthcare professionals should be careful about establishing a proper and reassuring relationship with patients and avoid criticizing them for preferring these methods. Patients should be informed about the use of phytotherapy, and be warned about its potential risks and side effects. <h3>Reference</h3> [1]Bahall M. Use of complementary and alternative medicine by patients with end-stage renal disease on haemodialysis in Trinidad: A descriptive study. BMC Complement Altern Med. 2017 May 4;17(1):250. doi: 10.1186/s12906-017-1755-7. PMID: 28472987; PMCID: PMC5418726. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0457 ASSOCIATION BETWEEN METHOTREXATE USE AND LYMPHOMA IN RHEUMATOID ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW
Authors: S. A. Alexander, D. Louden, G. Hughes, G. A. Starkebaum, N. Singh
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid Arthritis (RA) is associated with an increased risk of lymphoma compared to the general population, which has been attributed to increased disease activity (1, 2). By decreasing RA disease activity, methotrexate could potentially help to reduce the risk of lymphoma development; however, there are conflicting data in the literature. <h3>Objectives</h3> To perform systematic literature review to evaluate the association between use of methotrexate in RA and the risk of developing lymphoma. <h3>Methods</h3> A systematic literature search was performed using the PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception through December 9, 2021. The search was limited to observational studies and randomized controlled trials (RCT) published in English that evaluated the association between use of MTX in RA and the development of lymphoma. Case series and reports were excluded. Two authors independently extracted data from final articles using a predefined data abstraction form and conflicts were resolved by a third reviewer. Quality assessments were performed. <h3>Results</h3> The study identification and selection process are summarized in <b>Figure 1.</b> Of the initial 839 articles identified, only eight articles met the eligibility criteria. The characteristics of these studies are depicted in <b>Table 1</b>. These were mostly observational studies except one RCT. Study sample sizes varied from 160 to 20,000 patients with RA. Five studies reported the odds/hazards ratio of occurrence of lymphoma in patients exposed to methotrexate versus not exposed to methotrexate. Three studies compared risk of lymphoma development in RA patients treated with methotrexate versus other biological DMARD of which one was an RCT. Most of the studies adjusted for variables such as age, sex, RA disease activity measures and inflammatory markers, concomitant RA medications and risk factors for cancer and RA. Of the eight studies, six did not find a significant association between MTX use and lymphoma, while two studies, conducted in Japan, reported a significant association. Included studies were of moderate to high quality. The heterogeneity of the included studies precluded conducting a meta-analysis. <h3>Conclusion</h3> While there are conflicting data regarding the role of MTX in lymphomagenesis in RA, we observed that a majority of high-quality epidemiologic studies did not support an association between MTX use and development of lymphoma. Only two studies from Japan reported an association between MTX use and development of lymphoma. <h3>References</h3> [1]Baecklund E, et al. Lymphoma development…the driving forces? Seminars in cancer biology; 2014: Elsevier. p. 61-70. [2]Smitten AL, et al. A meta-analysis of the…rheumatoid arthritis. Arthritis research &amp; therapy. 2008;10(2):1-8. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0180 ACR20 RESPONSE AS SURROGATE OF ACR70 RESPONSE IN RHEUMATOID ARTHRITIS: A TRIAL-LEVEL ANALYSIS FROM A SYSTEMATIC REVIEW OF RANDOMIZED TRIALS
Authors: A. Ah Koon, C. Confavreux, G. Grenet, S. Mainbourg, J. P. Larbre, F. Coury, J. C. Lega, E. Massy
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The approval by medicines regulatory agencies of new therapeutic agents in rheumatoid arthritis (RA) is based on results of phase III randomized controlled trials. The RA trials have been mainly used ACR20 response as primary endpoint. Conversely, this outcome is not clinically relevant for significant improvement of patient's quality of lile. <h3>Objectives</h3> We aimed to explore the surrogacy between ACR20 and ACR70 in rheumatoid arthritis. <h3>Methods</h3> We performed a systematic review search by screening randomized clinical trials registered in MEDLINE, EMBASE and the Cochrane Library between January 1990 and June 2021. We included all randomized trials (phase II and III trials, including multiarm design) that compared biotherapies or JAK inhibitors with csDMARDs or placebo with available ACR20 and ACR70 response. The coefficient of determination R2trial between these two outcomes were estimated using weighted metaregression. To validate the surrogacy, the coefficient of determination (R²trial) should be superior than 0.65 and close to 1. The lower limit of 95% prediction interval needed to be upper than 0.5 to predict a weak surrogacy and upper than 0.72 to predict a strong surrogacy. The 95% prediction interval for R2trial was calculated with the percentile bootstrapping method. <h3>Results</h3> We included 189 randomized trials totalizing 81,734 patients. Using 322 comparisons, the coefficient of determination R²trial for estimating the relation between ACR20 on ACR70 responses is 0.55 (95% prediction interval 0.47-0.63). In subgroup analyses, the R²trial for the anti-TNF therapeutic class was 0.69 (95% prediction interval 0.56-0.78). The R²trial in other subgroup analyses (double-blind design, superiority studies, multicentric studies, year of publication, corticosteroid use, small-study effect, and other therapeutic classes) were not relevant for surrogacy. <h3>Conclusion</h3> There is no surrogacy between ACR20 and ACR70 in RA. The use of ACR20 as primary outcomes should be limited to phase II trials and is not suitable for health technology assessment of benefit-risk ratio. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0184 U-SHAPED ASSOCIATION OF SERUM URATE WITH ALL-CAUSE MORTALITY IN GOUT PATIENTS: NHANES 2007-2018
Authors: N. Chen, Q. H. LI, S. X. Hu, H. Lin, L. Dai
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The EULAR guideline for the management of gout recommended a target serum urate (sUA) level of less than 6 mg/dl in gout patients and less than 5 mg/dl in tophaceous gout patients [1]. This recommendation is based on the evidence that achieving these targets will reduce gout attacks and tophi size. However, less is known about the impact of sUA on mortality in gout patients. <h3>Objectives</h3> To explore the relationship between sUA level and all-cause mortality in gout patients. <h3>Methods</h3> The present prospective cohort study included participants 20 years or older with gout enrolled from the 2007-2008 through 2017-2018 annual NHANES cycles. The data of mortality and its underlying causes to 31 December 2019 were obtained from the National Death Index records. The relationship of gout patients between sUA level and mortality were analyzed by Cox proportional hazards analysis, the restricted cubic spline regression analysis and two piece-wise regression model. <h3>Results</h3> A total of 1442 gout patients were included with median follow-up period 63 (interquartile range, 33-102) months. Compared with gout patients with sUA less than 6mg/dl, gout patients with sUA&gt;6mg/dl were characterized by greater age, more often men, higher BMI and higher prevalence of hyperlipidemia (P &lt;0.05). Cox proportional hazards analysis showed that sUA was a risk factor of mortality (HR 1.09, 95% CI 1.02 to 1.16) after adjusted by age, sex, race, education, BMI, smoking, cardiovascular disease, hyperlipidemia, hypertension and diabetes mellitus. However, restricted cubic spline regression analysis showed a U-shaped relationship between sUA and all-cause mortality (Pnon-linear &lt;0.001, Figure 1). Two piece-wise regression model revealed sUA level of 6.2 mg/dl corresponded to the lowest mortality risk. For those patients with sUA less than 6mg/dl, the risk of all-cause death was borderline reduced 12% (HR 0.88, 95% CI 0.72 to 1.07) with each sUA unit increase. After 6 mg/dl, the risk of all-cause death increased 26% (HR 1.26, 95% CI 1.14 to 1.40) for each sUA unit increase. <h3>Conclusion</h3> There is a U-Shaped association of sUA with all-cause mortality in gout patients. Target sUA of less than 6 mg/dl is rational as it corresponds to the interval of lowest mortality. Randomized trials with mortality as an endpoint are warranted to determine target sUA for gout patients. <h3>Reference</h3> [1]Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017 Jan;76(1):29-42. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0047 THE COMPLEMENT FACTOR H-RELATED PROTEIN-5 EXACERBATES PATHOLOGICAL BONE FORMATION OF ANKYLOSING SPONDYLITIS
Authors: C. N. Son, J. Lee, S. Jo, I. H. Sung, T. H. Kim
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The complement factor H-related protein-5 (FHR-5), a member of the human factor H protein family, enhances complement activation. The influence of complement activation on bone and joint was recognized in bone fracture healing, arthritis, and osteomyelitis. Recently, FHR-5 has been linked to eye, kidney, infection, cancer and autoimmune diseases. FHR-5 was also significantly up-regulated in proteomic analysis of serum and synovial fluid for ankylosing spondylitis (AS). <h3>Objectives</h3> We aimed to evaluate whether FHR-5 exacerbates bone inflammation and ectopic formation of AS. <h3>Methods</h3> The study included 65 patients with AS and 25 healthy controls (HC). Collected sera were divided into three groups according to HC, two AS groups (low CRP and high CRP) based on the CRP 0.8. Human TNF, IL6, IL-17, IL-23, and FHR-5 in three groups were measured with ELISA and human FHR-5 levels were compared to TNF, IL-6, IL-17, and IL-23 levels. In addition, soluble FHR-5 proteins were administered with Curdlan-injected SKG mice 2 time for a week and monitored for 5 weeks <i>In vivo</i> model. Foot and ankle were evaluated by micro-CT, Hematoxylin and Eosin for histological observation, and Safranin O for cartilages. Moreover, these finding were further assessed in the AS-osteoprogenitor <i>In vitro</i> model. <h3>Results</h3> In consistent with human data, proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) and CFHR5 were elevated in AS group compared to HC group. FHR5 levels were not significantly correlated with proinflammatory cytokines, whereas FHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble FHR5 has no effect on clinical arthritis scores and thickness at hindpaw in Curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of ankle as revealed by micro-CT image and quantification. Basal FHR5 expression was upregulated in AS-osteoprogenitors compared to control cells. Also, treatment with FHR5 remarkedly induced bone mineralization status of AS-osteoprogenitors during osteogenic differentiation accompanied by MMP13 expression. <h3>Conclusion</h3> We provide the first evidence demonstrating that FHR-5 can exacerbate pathological bone formation of AS. Therapeutic modulation of FHR-5 could be promising for future treatment of AS. <h3>Reference</h3> [1]Lee et al, Clin Proteomics. 2020 Jun 1;17:20. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0325 RHEUMATOID ARTHRITIS PATIENTS AND WEATHER PATTERNS: A RHUMADATA™ STUDY OF 14,200 PATIENT-REPORTED OUTCOMES MATCHED WITH METEOROLOGICAL DATA
Authors: M. Joly-Chevrier, L. Coupal, L. Choquette Sauvageau, D. Choquette
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Anecdotally, patients with rheumatoid arthritis (RA) report seasonal changes in their symptoms. Anatomically, atmospheric pressure variations are captured by baroreceptors, which may generate this perception. <h3>Objectives</h3> To correlate seasonal changes with subjective assessment scores. <h3>Methods</h3> Environment Canada provided meteorological data from 2015 to 2020 for Montreal (Dorval). Hourly measurements of temperature, relative humidity, and pressure were available. We matched daily meteorological data with patient-reported pain (PtP), fatigue (PtF), and disease activity (PtGA) assessments from RHUMADATA™ participants. We calculated daily means, minimums, and maximums, as well as changes from the previous day for the winter and summer months. For the years 2015 to 2020, Pearson Correlation Coefficients (PCCs) were computed between Patient Reported Outcomes (PROs) and weather measurements. Optimal regression models (OM) were derived based on Akaike's Information Criteria (AIC). <h3>Results</h3> RA patients' PROs were matched with meteorological data (7411 winter measurements and 6789 summer measurements). At the time of the first PRO assessment, the mean age and disease duration were 60.1(13.5) and 10.5 (10.4), and 74.6% of patients were women. Patients provided an average of 14 PROs. In winter, PtP, PtF and PtGA were 3.48 (2.79), 3.49 (2.96) and 3.42 (2.66), and 3.45 (2.81), 3.46 (2.96) and 3.33 (2.63) in summer. PtGA was statistically higher in winter (p-value=0.0379). PCC and OMs are shown in Table 1. In winter, all correlations are very weak (less than 0.19). PtGA is not correlated with any weather measures in both winter and summer. PtP and PtF correlate with some weather measures in both seasons. <h3>Conclusion</h3> In this study of 14200 wheather-matched PROs, mean PtP, PtF, and PtGA scores are higher in winter among RA patients, but the differences are small. Few meteorological measures are significantly correlated with PROs, and all correlations are very weak. Meteorological variables explain a quite small percentage of the variation in PRO variation (small R-square). No consistent relationship between PROs and meteorological conditions is reported by other smaller studies. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Maxine Joly-Chevrier: None declared, Louis Coupal: None declared, Loïc Choquette Sauvageau: None declared, Denis Choquette Speakers bureau: Abbvie, Amgen, Eli Lilly, Fresenius Kabi, Novartis, Pfizer, Sandoz, Tevapharm, Consultant of: Abbvie, Amgen, Eli Lilly, Fresenius Kabi, Novartis, Pfizer, Sandoz, Tevapharm, Grant/research support from: Abbvie, Amgen, Eli Lilly, Fresenius Kabi, Novartis, Pfizer, Sandoz, Tevapharm.